a companion to the philosophy of biology (blackwell companions to philosophy)

1. A Companion to the Philosophy of Biology

2. Blackwell Companions to Philosophy This outstanding student reference series offers a comprehensive and authoritative survey of philosophy as a whole. Written by todays leading philosophers, each volume provides lucid and engaging coverage of the key gures, terms, topics, and problems of the eld. Taken together, the volumes provide the ideal basis for course use, representing an unparalleled work of reference for students and specialists alike. Already published in the series: 1. The Blackwell Companion to Philosophy, Second Edition Edited by Nicholas Bunnin and Eric Tsui-James 2. A Companion to Ethics Edited by Peter Singer 3. A Companion to Aesthetics Edited by David Cooper 4. A Companion to Epistemology Edited by Jonathan Dancy and Ernest Sosa 5. A Companion to Contemporary Political Philosophy (2 Volume Set), Second Edition Edited by Robert E. Goodin and Philip Pettit 6. A Companion to Philosophy of Mind Edited by Samuel Guttenplan 7. A Companion to Metaphysics Edited by Jaegwon Kim and Ernest Sosa 8. A Companion to Philosophy of Law and Legal Theory Edited by Dennis Patterson 9. A Companion to Philosophy of Religion Edited by Philip L. Quinn and Charles Taliaferro 10. A Companion to the Philosophy of Language Edited by Bob Hale and Crispin Wright 11. A Companion to World Philosophies Edited by Eliot Deutsch and Ron Bontekoe 12. A Companion to Continental Philosophy Edited by Simon Critchley and William Schroeder 13. A Companion to Feminist Philosophy Edited by Alison M. Jaggar and Iris Marion Young 14. A Companion to Cognitive Science Edited by William Bechtel and George Graham 15. A Companion to Bioethics Edited by Helga Kuhse and Peter Singer 16. A Companion to the Philosophers Edited by Robert L. Arrington 17. A Companion to Business Ethics Edited by Robert E. Frederick 18. A Companion to the Philosophy of Science Edited by W. H. Newton-Smith 19. A Companion to Environmental Philosophy Edited by Dale Jamieson 20. A Companion to Analytic Philosophy Edited by A. P. Martinich and David Sosa 21. A Companion to Genethics Edited by Justine Burley and John Harris 22. A Companion to Philosophical Logic Edited by Dale Jacquette 23. A Companion to Early Modern Philosophy Edited by Steven Nadler 24. A Companion to Philosophy in the Middle Ages Edited by Jorge J. E. Gracia and Timothy B. Noone 25. A Companion to African-American Philosophy Edited by Tommy L. Lott and John P. Pittman 26. A Companion to Applied Ethics Edited by R. G. Frey and Christopher Heath Wellman 27. A Companion to the Philosophy of Education Edited by Randall Curren 28. A Companion to African Philosophy Edited by Kwasi Wiredu 29. A Companion to Heidegger Edited by Hubert L. Dreyfus and Mark A. Wrathall 30. A Companion to Rationalism Edited by Alan Nelson 31. A Companion to Ancient Philosophy Edited by Mary Louise Gill and Pierre Pellegrin 32. A Companion to Pragmatism Edited by John R. Shook and Joseph Margolis 33. A Companion to Nietzsche Edited by Keith Ansell Pearson 34. A Companion to Socrates Edited by Sara Ahbel-Rappe and Rachana Kamtekar 35. A Companion to Phenomenology and Existentialism Edited by Hubert L. Dreyfus and Mark A. Wrathall 36. A Companion to Kant Edited by Graham Bird 37. A Companion to Plato Edited by Hugh H. Benson 38. A Companion to Descartes Edited by Janet Broughton and John Carriero 39. A Companion to the Philosophy of Biology Edited by Sahotra Sarkar and Anya Plutynski Forthcoming 40. A Companion to Hume Edited by Elizabeth S. Radcliffe 41. A Companion to Aristotle Edited by Georgios Anagnostopoulos

3. A Companion to the Philosophy of Biology Edited by Sahotra Sarkar and Anya Plutynski

4. 2008 by Blackwell Publishing Ltd except for editorial material and organization 2008 by Sahotra Sarkar and Anya Plutynski BLACKWELL PUBLISHING 350 Main Street, Malden, MA 02148-5020, USA 9600 Garsington Road, Oxford OX4 2DQ, UK 550 Swanston Street, Carlton, Victoria 3053, Australia The right of Sahotra Sarkar and Anya Plutynski to be identied as the authors of the editorial material in this work has been asserted in accordance with the UK Copyright, Designs, and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs, and Patents Act 1988, without the prior permission of the publisher. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks, or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. First published 2008 by Blackwell Publishing Ltd 1 2008 Library of Congress Cataloging-in-Publication Data A companion to the philosophy of biology / edited by Sahotra Sarkar and Anya Plutynski. p. cm. (Blackwell companions to philosophy ; 39) Includes bibliographical references and index. ISBN 978-1-4051-2572-7 (hardcover : alk. paper) 1. BiologyPhilosophy. I. Sarkar, Sahotra. II. Plutynski, Anya. QH331.C8423 2006 570.1dc22 2007024735 A catalogue record for this title is available from the British Library. Set in 10 on 12.5 pt Photina by SNP Best-set Typesetter Ltd., Hong Kong Printed and bound in Singapore by Utopia Press Pte Ltd The publishers policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. For further information on Blackwell Publishing, visit our website at www.blackwellpublishing.com

5. v Contents List of Figures viii List of Tables x Notes on Contributors xi Acknowledgments xvii Introduction xviii Sahotra Sarkar and Anya Plutynski Part I Molecular Biology and Genetics 1 1 Gene Concepts 3 Hans-Jrg Rheinberger and Staffan Mller-Wille 2 Biological Information 22 Stefan Artmann 3 Heredity and Heritability 40 Richard C. Lewontin 4 Genomics, Proteomics, and Beyond 58 Sahotra Sarkar Part II Evolution 75 5 Darwinism and Neo-Darwinism 77 James G. Lennox 6 Systematics and Taxonomy 99 Marc Ereshefsky 7 Population Genetics 119 Christopher Stephens 8 The Units and Levels of Selection 138 Samir Okasha

6. contents vi 9 Molecular Evolution 157 Michael R. Dietrich 10 Speciation and Macroevolution 169 Anya Plutynski 11 Adaptationism 186 Peter Godfrey-Smith and Jon F. Wilkins Part III Developmental Biology 203 12 Phenotypic Plasticity and Reaction Norms 205 Jonathan M. Kaplan 13 Explaining the Ontogeny of Form: Philosophical Issues 223 Alan C. Love 14 Development and Evolution 248 Ron Amundson Part IV Medicine 269 15 Self and Nonself 271 Moira Howes 16 Health and Disease 287 Dominic Murphy Part V Ecology 299 17 Population Ecology 301 Mark Colyvan 18 Complexity, Diversity, and Stability 321 James Justus 19 Ecosystems 351 Kent A. Peacock 20 Biodiversity: Its Meaning and Value 368 Bryan G. Norton Part VI Mind and Behavior 391 21 Ethology, Sociobiology, and Evolutionary Psychology 393 Paul E. Grifths 22 Cooperation 415 J. McKenzie Alexander 23 Language and Evolution 431 Derek Bickerton

7. contents vii Part VII Experimentation, Theory, and Themes 453 24 What is Life? 455 Mark A. Bedau 25 Experimentation 472 Marcel Weber 26 Laws and Theories 489 Marc Lange 27 Models 506 Jay Odenbaugh 28 Function and Teleology 525 Justin Garson 29 Reductionism in Biology 550 Alexander Rosenberg Index 568

8. viii Figures Figure 2.1 Schematic diagram of a general communication system. 24 Figure 3.1 Norms of reaction of eye size as a function of temperature for three different genotypes of Drosophila melanogaster. 42 Figure 3.2 Growth of clones of Achillea millefolium at three different elevations. 43 Figure 3.3 Four different models of the determination of phenotype. 45 Figure 3.4 Hypothetical norms of reaction for two genotypes and the phenotypic distribution resulting from variation in the environment and genetic variation. 55 Figure 6.1 Phylogenetic trees. 105 Figure 6.2 Speciation by cladogenesis and anagenesis. 108 Figure 6.3 A phylogenetic tree of lizards, snakes, crocodiles, and birds. 109 Figure 6.4 Two cladograms of the same taxa. 111 Figure 12.1 Phenotypic plasticity and reaction norms. 206 Figure 12.2 Developmental sensitivity versus developmental conversion. 210 Figure 12.3 A developmental reaction norm visualization of buffering. 216 Figure 12.4 Developmental stability versus phenotypic plasticity. 217 Figure 13.1 Different mechanisms of morphogenesis. 228 Figure 15.1 A two signal model of T helper lymphocyte activation. 277 Figure 15.2 Idiotypic interactions between antibodies. 279 Figure 21.1 The hydraulic model of instinctual motivation. 395 Figure 21.2 The Prisoners Dilemma. 401 Figure 21.3 Two versions of the Wason card selection task, one an abstract problem and the other a problem concerning social exchange. 403 Figure 22.1 The Prisoners Dilemma payoffs. 416 Figure 22.2 Reciprocity changes the Prisoners Dilemma into an Assurance Game. 421 Figure 22.3 The payoff matrix for cooperative behavior generated through byproduct mutualism. 425 Figure 22.4 The spatial prisoners dilemma illustrating the evolution of stable cooperative regions. 427

9. ix Figure 22.5 The spatial prisoners dilemma illustrating the evolution of stable cooperative regions. 427 Figure 22.6 The Spatial Prisoners Dilemma. 428 gures

10. x Tables Table 15.1 Some of the main cell types of the immune system. 273 Table 18.1 Different concepts of ecological stability. 340 Table 23.1 Incongruous properties of language and ACSs. 435

11. xi Notes on Contributors J. McKenzie Alexander is at the Department of Philosophy, Logic and Scientic Method at the London School of Economics and Political Science. His interests are in Evolutionary game theory, philosophy of social science, and rational choice theory. Recent publications include, Follow the leader: local interactions with inuence neigh- borhoods, Philosophy of Science, 72, 86113 (2005), Random Boolean networks and evolutionary games, Philosophy of Science, 70, 12891304 (2003),Bargaining with neighbours: Is justice contagious? (with Brian Skyrms), Journal of Philosophy, 96 (11), 58898 (1999), and The Structural Evolution of Morality (Cambridge: Cambridge University Press, 2007). Ron Amundson is Professor, Dept of Philosophy, University of Hawaii at Hilo. His research is in history and philosophy of biology, as well as bioethics and disability rights. Recent publications include: Bioethics and disability rights: conicting values and perspectives, (with Shari Tresky) in press, and The Changing Role of the Embryo in Evolutionary Thought: Roots of Evo-Devo (Cambridge: Cambridge University Press, 2005). Stefan Artmann is at the Institute of Philosophy, Friedrich-Schiller-University Jena. In 2007, he nished his postdoctoral thesis on the philosophy of structural sciences (such as information theory, cybernetics, and decision theory). He has published several papers on questions related to the application of information theory and semiotics to biological systems, e.g., Articial life as a structural science, Philosophia naturalis, 40, 183205 (2003), Biosemiotics as a structural science: between the forms of life and the life of forms, Journal of Biosemiotics, 1, 183209 (2005), and Computing codes versus interpreting life. Two alternative ways of synthesizing biological knowledge through semiotics, in M. Barbieri (Ed.), Introduction to Biosemiotics (Dordrecht: Springer, 2007), pp. 20933. Mark A. Bedau is Professor of Philosophy and Humanities at Reed College in Portland, Oregon. He is also Editor-in-Chief of the journal Articial Life (MIT Press); co-founder of the European Center for Living Technology, a research institute in Venice, Italy, that

12. notes on contributors xii investigates theoretical and practical issues associated with living systems; and co- founder of ProtoLife SRL, a start-up company with the long-term aim of creating useful articial cells. He has published and lectured around the world extensively on philosophical and scientic issues concerning emergence, evolution, life, mind, and the social and ethical implications of creating life from scratch. Derek Bickerton is Professor Emeritus of Linguistics at the University of Hawaii. He is best known for his work on Creole languages, leading to the Language Bioprogram Hypothesis, and his subsequent work on the evolution of language. Among his books are Roots of Language, Language and Species, and Language and Human Behavior. Mark Colyvan is Professor of Philosophy and Director of the Sydney Centre for The Foundations of Science at the University of Sydney in Sydney, Australia. He has published on the philosophy of mathematics, philosophy of science (especially ecology and conservation biology), philosophy of logic, and decision theory. His books include The Indispensability of Mathematics (OUP, 2001) and, with Lev Ginzburg, Ecological Orbits: How Planets Move and Populations Grow (OUP, 2004). Michael R. Dietrich is an Associate Professor in the Department of Biology at Dartmouth College. Marc Ereshefsky is Professor of Philosophy at the University of Calgary. He has written extensively on biological taxonomy and has published two books on the topic, The Poverty of the Linnaean Hierarchy and The Units of Evolution. His current research focuses on biological homology and its philosophical applications. Justin Garson is a lecturer in Philosophy at the University of Texas at Austin. His interests are in the Philosophy of Science, with emphasis on the history and philosophy of neuroscience and psychiatry. He was one of the assistant editors of, and contributors to, The Philosophy of Science: An Encyclopedia (Routledge, 2005). Recent publications include The introduction of information into neurobiology. Philosophy of Science, 70, 92636 (2003). Peter Godfrey-Smith is Professor of Philosophy at Harvard University, but also spends time at the Philosophy Program, Research School of Social Sciences, The Australian National University. Godfrey-Smiths primary research interests are in the philosophy of biology and philosophy of mind. He also has interests in other parts of philosophy of science, causation, and the philosophy of John Dewey. His books include: Complexity and the Function of Mind in Nature (Cambridge: Cambridge University Press, 1996) and Theory and Reality: An Introduction to the Philosophy of Science (Chicago: University of Chicago Press, 2003). Paul E. Grifths is a philosopher of science with a focus on biology and psychology, and was educated at Cambridge and the Australian National University. He taught at Otago University in New Zealand and was later Director of the Unit for History and Philosophy of Science at the University of Sydney, before taking up a professorship in the Department of History and Philosophy of Science at the University of Pittsburgh.

13. notes on contributors xiii He returned to Australia in 2004, rst as an Australian Research Council Federation Fellow and then as University Professorial Research Fellow at the University of Sydney. He is a Fellow of the Australian Academy of the Humanities. Moira Howes is Associate Professor of Philosophy at Trent University. She specializes in metaphysics, philosophy of science (especially immunology), and feminist epistemology. Her current research concerns immunological models of the human female repro- ductive tract. James Justus wrote a dissertation on The Stability-Diversity-Complexity Debate of Theoretical Community Ecology: A Philosophical Analysis at the University of Texas, Austin. He has published in the journals Biology and Philosophy, Conservation Biology, and Philosophy of Science. Recent publications include Qualitative scientic modeling and crop analysis, Philosophy of Science (2005); and Ecological and Lyapunov stability, Philosophy of Science (2007). His interests outside the philosophy of science include the history of analytic philosophy, environmental philosophy, logic and philosophy of mathematics, formal epistemology, and bird watching. Jonathan M. Kaplan, an Associate Professor of Philosophy at Oregon State University, specializes in the Philosophy of Biology, Philosophy of Science and Political Philosophy. In addition to various articles and book chapters, he has published two books, most recently Making Sense of Evolution: The Conceptual Foundations of Evolutionary Biology, co-authoredwithevolutionarybiologistMassimoPigliucci(Chicago:ChicagoUniversity Press, 2006). Marc Lange is Professor of Philosophy at the University of North Carolina at Chapel Hill. He is the author of Natural Laws in Scientic Practice (Oxford, 2000), An Introduction to the Philosophy of Physics: Locality, Fields, Energy, and Mass (Blackwell, 2002), and Laws and Lawmakers (Oxford, forthcoming). James Lennox is Professor at the Department of History and Philosophy of Science at the University of Pittsburgh. Research specialties include Ancient Greek philosophy, science and medicine, and Charles Darwin and Darwinism. Lennox has published essays on the philosophical and scientic thought of Plato, Aristotle, Theophrastus, Boyle, Spinoza, and Darwin, especially focused on scientic explanation, and particularly teleological explanation, in the biological sciences. He is author of Aristotles Philosophy of Biology (Cambridge 2000) and Aristotle on the Parts of Animals IIV (Oxford, 2001), the rst English translation of this work since 1937. He is co-editor of Philosophical Issues in Aristotles Biology (Cambridge, 1987); Self-Motion from Aristotle to Newton (Princeton, 1995); and Concepts, Theories, and Rationality in the Biological Sciences (Pittsburgh and Konstanz, 1995). Richard C. Lewontin is Alexander Agassiz Research Professor at the Museum of Comparative Zoology, Harvard University. He is an evolutionary biologist, geneticist, and pioneer in the application of techniques from molecular biology to questions of genetic variation and evolution. He is the author of The Genetic Basis of Evolutionary

14. notes on contributors xiv Change and Biology as Ideology, and the co-author of The Dialectical Biologist (with Richard Levins) and Not in Our Genes (with Steven Rose and Leon Kamin). Alan C. Love is Assistant Professor of Philosophy at the University of Minnesota. His current work focuses on the nature of conceptual change and explanation in the biological sciences, specically within the dynamic of the discipline of evolutionary developmental biology, using a combination of historical and philosophical methodologies. Selected Publications include Evolutionary morphology and evo-devo: hierarchy and novelty, Theory in Biosciences, 124, 31733 (2006), Evolvability, dispositions, and intrinsicality, Philosophy of Science, 70(5), 101527 (2003), and Evolutionary morphology, innovation, and the synthesis of evolutionary and developmental biology, Biology and Philosophy, 18, 30945 (2003). Staffan Mller-Wille received his PhD in Philosophy from the University of Bielefeld for his dissertation on Linnaeus taxonomy. He worked at the Max-Planck-Institute for the History of Science (Berlin) from 2000 to 2004 and is currently holding a post as Senior Research Fellow for Philosophy of Biology at the University of Exeter. He is author of the book Botanik und weltweiter Handel (1999) and has published articles on the history and epistemology of natural history, genetics, and anthropology. Dominic Murphy is Assistant Professor of Philosophy at Caltech. He is the author of Psychiatry in the Scientic Image (MIT, 2006), as well as papers in the philosophy of mind and the philosophy of biology. Bryan G. Norton is Professor in the School of Public Policy, Georgia Institute of Technology and author of Why Preserve Natural Variety? (Princeton University Press, 1987),TowardUnityAmongEnvironmentalists(OxfordUniversityPress,1991),Searching for Sustainability (Cambridge University Press, 2003), and Sustainability: A Philosophy of Adaptive Ecosystem Management (University of Chicago Press, 2005). Norton has contributed to journals in several elds and has served on the Environmental Economics Advisory Committee of the US EPA Science Advisory Board, and two terms as a member of the Governing Board of the Society for Conservation Biology. His current research concentrates on sustainability theory and on spatio-temporal scaling of environmental problems. He was a member of the Board of Directors of Defenders of Wildlife from 1994 to 2005 and continues on their Science Advisory Board. Jay Odenbaugh is a member of the Department of Philosophy and Environmental Studies Program at Lewis and Clark College. His main areas of research are in the philosophy of science (especially ecology and evolutionary biology) and environmental ethics. He is currently working on a book tentatively entitled On the Contrary: A Philosophical Examination of the Environmental Sciences and their Critics examining these issues especially in ecology, climatology, and environmental economics. Samir Okasha received his doctorate from the University of Oxford in 1998 and is currently Reader in Philosophy of Science at the University of Bristol. He has published numerous research articles in journals such as Philosophy of Science, Evolution, British

15. notes on contributors xv Journal for the Philosophy of Science, Synthese, Biology and Philosophy, and others. He is currently completing a monograph on the units of selection debate to be published by Oxford University Press. Kent A. Peacock is Associate Professor of Philosophy at the University of Lethbridge, Alberta, Canada. He has published in philosophy of physics and ecology, and is the editor of a text, Living With the Earth: An Introduction to Environmental Philosophy (Toronto: Harcourt Brace, 1996). Anya Plutynski is an Assistant Professor of Philosophy at the University of Utah. Her research is in the history and philosophy of biology. She is the author of several recent articles and book chapters on the early synthesis and evolutionary explanation, in some of the following journals: Proceedings of the Philosophy of Science, British Journal of Philosophy of Science, Biology and Philosophy, and Biological Theory. Hans-Jrg Rheinberger is Director at the Max Planck Institute for the History of Science in Berlin and a Scientic Member of the Max Planck Society. He studied philosophy (MA) and biology (PhD) at the University of Tbingen and the Free University of Berlin. He worked as a molecular biologist at the Max Planck Institute for Molecular Genetics in Berlin, and as a historian of science at the Univer- sities of Lbeck and Salzburg. Among his books are Toward a History of Epistemic Things (1997), Iterationen (2005), Epistemologie des Konkreten (2006) and Historische Epistemologie zur Einfhrung (2007). He is also a co-editor of The Concept of the Gene in Development and Evolution (2000), and The Mapping Cultures of Twentieth Century Genetics (2004). Alex Rosenberg is the R. Taylor Cole Professor of Philosophy, and co-Director of the Center for Philosophy of Biology, Duke University. His interests focus on problems in metaphysics, mainly surrounding causality, the philosophy of social sciences, especially economics, and most of all, the philosophy of biology, in particular the relationship between molecular, functional, and evolutionary biology. Recent publications include: Darwinian Reductionism: Or, How to Stop Worrying and Love Molecular Biology (University of Chicago, 2006). Sahotra Sarkar is Professor of Integrative Biology, Geography and the Environment, and Philosophy at the University of Texas at Austin. His research is in history and philosophy of science, formal epistemology, philosophy of biology, and conservation biology. Recent books include Doubting Darwin? Creationist Designs on Evolution (Blackwell,2007),BiodiversityandEnvironmentalPhilosophy:AnIntroduction(Cambridge, 2005), and Molecular Models of Life (MIT, 2005). Christopher Stephens is Assistant Professor of Philosophy at University of British Columbia. Dr Stephens specializes in philosophy of biology, philosophy of science, and epistemology. Recent publications include Modelling reciprocal altruism, British Journal for the Philosophy of Science (1996) and When is it selectively advantageous to have true beliefs? Philosophical Studies (2001). His current research interests include

16. notes on contributors xvi drift and chance in evolutionary biology, the evolution of rationality, and the relationship between prudential and epistemic rationality. Marcel Weber received an MSc in molecular biology from the University of Basel, a PhD in philosophy at the University of Konstanz, and a Habilitation in philosophy at the University of Hannover. He is currently Swiss National Science Foundation Professor of Philosophy of Science at the University of Basel. His books include Philosophy of Experimental Biology (Cambridge University Press, 2005) and Die Architektur der Synthese: Entstehung und Philosophie der modernen Evolutionstheorie (Walter de Gruyter, Berlin, 1998). Jon F. Wilkins is Research Professor at the Santa Fe Institute. His research interests include coalescent theory, genomic imprinting, human demographic history, altruism, and cultural evolution. Recent publications include: Gene genealogies in a continuous habitat: a separation of timescales approach, Genetics, 168, 222744 (2004); (with J. Wakeley) The coalescent in a continuous, nite, linear population, Genetics, 161, 87388 (2002); Genomic imprinting and methylation: epigenetic canalization and conict, Trends Genet., 21, 35665 (2005); and (with D. Haig) What good is genomic imprinting: the function of parent-specic gene expression, Nat. Rev. Genet., 4, 359 68 (2003).

17. xvii Acknowledgments The editors gratefully acknowledge all the contributors and the editors at Blackwell, especially Jeff Dean, for their efforts in completing this volume.

18. xviii Introduction sahotra sarkar and anya plutynski There are many different ways to do the philosophy of biology. At one end of a spectrum of possibilities would be works of general philosophical interest drawing on biological examples for illustration and support. At the other end would be works that deal only with conceptual and methodological issues that arise within the practice of biology. The strategy of this book is closer to the second way of approaching the subject. It aims to provide overviews of philosophical issues as they arise in a variety of areas of contemporary biology. Traditionally, evolution has been the focus of most philosophical attention. While it surely remains true that nothing in biology makes sense except in light of evolution (Dobzhansky, 1973), this tradition within the philosophy of biology is myopic insofar as it ignores much if not most of the work in contemporary biology. Intended primarily for students and beginning scholars, this book takes a wider perspective and addresses philosophical questions arising in molecular biology, developmental biology, immunology, ecology, and theories of mind and behavior. It also explores general themes in the philosophy of biology, for instance, the role of laws and theories, reductionism, and experimentation. In this respect, this book aims to break new ground in the philosophy of biology. Before we turn to what is new, let us briey look at the background from which contemporary philosophy of biology emerged. 1. Background When the logical empiricists reoriented the direction of philosophy of science in the 1920s and 1930s, the loci of their attention were mathematics (and within it, almost entirely mathematical logic) and physics (initially relativity theory, later also quantum mechanics). This not only set the agenda, but also the tone, for the philosophy of science. The relatively simple axiomatic structures of relativity theory and quantum mechanics or, at least, how professional philosophers conceived those elds became the yardstick of comparison for other disciplines. If these other disciplines were found to be less general in their intended domain, to be using different criteria of rigor (that is, using techniques different from the type of mathematics used in mathematical logic), or simply different, they were presumed to be wanting. This applied not only to biology

19. xix or chemistry (or, for that matter, the social sciences) but even to other areas of physics. Biology thus suffered from a not always benign neglect throughout this period. Yet, in spite of this limited attention, if the sophistication of the discussion is used as a standard, biology fared much better during the early decades of the logical empiricist regime (that is, from 1925 to 1945) than during the next 20 years. This is not only because many biologists including Driesch (1929), J. S. Haldane (1929, 1931), Hogben (1930), and J. B. S. Haldane (1936, 1939) explicitly debated philosophical positions, in particular, the relative roles of reductionism and holism in biology, during those decades. These debates within the biological community helped the development of philosophy of biology, but there were also signicant attempts by philosophers to come to terms with the exciting developments that had taken place in biology, particularly in genetics and evolution, during the rst three decades of the twentieth century. Woodger (1929) produced an exploration of traditional philosophical problems in biology, such as vitalism and mechanism, as well as a theory of biological explanation. In 1937 he went on to attempt to axiomatize parts of genetics.1 By 1952 Woodger (1952) had clearly articulated what, after independent formulation and elaboration by Nagel (1949, 1951, 1961), became the standard model of theory reduction.2 Nagel used this model in an attempt to explicate mechanistic explanation in biology. Less successfully, he attempted to provide a deationary account of teleological explanation in biology (Nagel, 1961, 1977). Arguably, until at least the 1960s, philosophers provided less philosophical insight about biology than theoretically oriented biologists. In the case of mechanistic explanation, for instance, as far as substantive biological questions are concerned, Nagel achieved little more than Hogben (1930). All he did was translate the simplest biological questions into the logical empiricists framework and presumed that the result showed what was philosophically interesting about biology. Following the standard twentieth-century philosophical tradition, Nagels writings on biology contributed little that scientists, even philosophically oriented biologists, found valuable. Nagel also displayed a strange refusal to follow contemporary developments in biology: between 1949 and 1961 he saw no reason to temper his bleak assessment of the state of mechanistic/reductionist explanation in biology the events of 1953 either completely slipped by him, or failed to impress him. The Structure of Science from 1961 has several sections devoted to reductionism in biology but makes no mention of the double helix or, for that matter, any other development in molecular biology that had raised the potential for successful reduction in biology to an entirely different level (Nagel, 1961). In the philosophy of biology, during the late 1950s and early 1960s only two notable exceptions stand out, Beckners The Biological Way of Thought and, especially, Goudges The Ascent of Life, the latter being a scientically fairly sophisticated philosophical exploration of evolutionary theory (Beckner, 1959; Goudge, 1961; see also 1 Woodger (1937), under the sway of operationalism and skepticism about theoretical entities, attempted an axiomatization of genetics without gene as a term; Carnap (1958) developed some of Woodgers formal treatment in more interesting ways. 2 For a history, see Sarkar (1989). introduction

20. xx Scriven, 1959). The situation changed for the better in the late 1960s and 1970s. Hull (1965, 1967, 1968) began to explore the conceptual structure of evolutionary biology. Wimsatt (1971, 1972) provided a detailed analysis of teleological explanation (and biological feedback), drawing extensively on contemporary work in theoretical biology. In a series of papers, Schaffner (1967a, b, 1969, 1976) began to argue the case for reductionism in molecular genetics while Hull (1972, 1974, 1976, 1981) questioned Schaffners assessment. Ruse (1976) and Wimsatt (1976) were among those who joined this debate. A consensus emerged against reductionism (provided that reduction was construed in the fashion inherited from Nagel and the logical empiricists). Philosophy of biology also played its part, though rather late, in the rejection of logical empiricism in the 1960s and 1970s. Since the early 1970s, the philosophy of biology has had a continuous and increas- ingly prominent presence in the philosophy of science. Occasional abuse of biology by philosophers has continued as late as 1974, Popper would claim that Darwinism is not a scientic enterprise (Popper, 1974). Over the years, however, philosophy of biology has contributed to the development of the various alternatives to logical empiricism, including scientic realism, the semantic view of theories, and, in particular, naturalistic epistemology. Within the general context of the philosophy of biology, the last of these programs has been particularly natural and fecund presumably because philosophers of biology, because of their engagement with biology, are more likely than other philosophers to analyze how humans are evolutionarily produced, constrained, and challenged, as biological organisms. In fact, barring a very few exceptions, there is consensus among philosophers of biology of the great value of the naturalized perspective in philosophy where naturalism is very narrowly construed purely in evolutionary terms. Moreover, philosophers of biology have quite routinely begun to practice biology. If philosophy is to be done in continuity with science, as Quine once urged, no area in philosophy has followed that dictum more systematically than the philosophy of biology. In the late 1970s, philosophy of biology became almost exclusively concerned with evolutionary theory. In some ways, this focus was productive; core philosophical questions were addressed about the foundations of evolutionary theory. For instance, Hull (1965a, b; see also Sober, 1988), advanced a discussion of different schools of phylogenetic analyses that has subsequently developed a rich literature on the methodological commitments of different schools of thought in systematics and phylogenetics. Philosophers including Wimsatt (1980), Brandon (1982), and Sober (1984) produced useful analyses of what constitutes the units of selection, while several prominent biologists, including Lewontin (1970) and Maynard Smith (1976), made important philosophical contributions. Sobers 1984 book, The Nature of Selection, advanced a clear analysis of the nature of laws and the structure of evolutionary theory, and particularly claried related questions about the units-of-selection debate. Another 1984 book of equal merit was Flews (1984) Darwinian Evolution. However, the almost exclu- sive focus on evolution in much of the literature of the late 1970s and 80s arguably hurt the development of the discipline. Many of the philosophical writings on biology from this period remained inattentive to molecular biology where, for better or for worse, most of biological research had become concentrated. Kitcher (1982, 1984) and Rosenberg (1985), however, are notable exceptions. Kitcher (1982) gave a thoughtful sahotra sarkar and anya plutynski

21. xxi analysis of the transformation of biology after 1953, as well as a critical discussion of gene concepts (Kitcher, 1984), and Rosenberg (1985) advanced a perspective that treated genetics and molecular biology as being central to biology. Given this state of the eld, it is easy to understand the molecular biologists lack of concern for philosophical critiques of their enterprise. This lack of concern was particularly noticeable during the debates over the initiation of the Human Genome Project in the late 1980s and early 1990s, a debate on which philosophers, unlike historians and social scientists, had no perceptible inuence. (A notable exception to these generalizations is neurobiology which has always received considerable philosophical attention though usually in the context of the philosophy of mind.) Since the early 1990s, in a very welcome development, philosophical writing on biology has extended its scope to cover many areas within biology beyond evolutionary theory.3 There has been much recent interest in ecology, molecular and developmental biology. There has also nally been some attention to the role of experimentation in biology. In particular, Rheinberger (1993, 1997) has pioneered the use of techniques from the continental tradition of philosophy in the analysis of experimentation in molecular biology. Philosophers of biology have usually also paid ample attention to the history of biology. With intellectual and technical history gradually falling out of fashion in the professional history of science, philosophers of biology have done much to keep the history of the science of biology alive in contemporary research. This book reects all these trends. 2. Structure of the Companion Most of biology today is molecular biology, and the Companion begins with a section on molecular biology and genetics (Molecular Biology and Genetics). Rheinberger and Mller-Wille (Gene Concepts) provide a historical review the various ways in which genes have been conceptualized, and how these have changed from the period of classical genetics to the post-genomic era in which we now nd ourselves. Artmann (Biological Information) explores the troubled question of whether and how biological information is susceptible to precise, quantitative measurement, an issue that has been hotly debated by philosophers (Godfrey-Smith, 2004; Sarkar, 2005). Contrary to many philosophers (Sarkar, 1996), he argues that there is more to informational talk in biology than mere metaphor. Lewontin (Heredity and Heritability) provides a philosophically sophisticated account of how classical genetics views heredity and adds a critique of the much- abused concept of heritability. Sarkar (Genomics, Proteomics, and Beyond) specu- lates on where the study of heredity and development is going in the wake of the massive whole-genome sequencing projects. Both Lewontin and Sarkar emphasize the limitations of a gene-centered view of biology and argue for a more developmentally oriented approach to understanding the emergence of phenotypes. The next section (Evolution) turns to a number of classic issues addressed in the philosophy of biology, as well as some issues that have not perhaps received the atten- 3 The textbook by Sterelny and Grifths (1999) is indicative of this trend. introduction

22. xxii tion they deserved. Reconciling Darwins own views with the various ways in which Darwinism has been understood during the last 130 years has been a challenge for biologists, historians, and philosophers of biology. Lennox (Darwinism and Neo- Darwinism) identies the core principles of Darwins original theory, and traces their empirical and conceptual development through the evolutionary synthesis, arguing that there is a meaningful set of commitments one can identify as Darwinian. A further classic problem in evolutionary biology is how species should be dened and classied. Ereshefsky (Systematics and Taxonomy) analyzes a variety of controversies that have arisen among biologists and philosophers of biology about the nature of species and their classication, ultimately defending a pluralist view of how species should be dened. Population genetics has typically been viewed as the theoretical core of evolutionary biology. Stephens (Population Genetics) recounts the history of the origins of population genetics, and reviews central debates in the history of the theory. He also considers a number of conceptual issues about representation and explanation that arise in the context of theoretical population genetics. Okasha (Units and Levels of Selection) reviews the conceptual as well as empirical issues at stake in the debate over the units and levels of selection and gives a history of the debate from Darwin to the present day. He shows how this debate is tied to concerns about the evolution of altruism, the plau- sibility of group and kin selection, species selection and macroevolution, and concludes with a review of multilevel selection theory. Dietrich (Molecular Evolution) describes the rise of the neutral theory of molecular evolution, and discusses how debates over drift versus selection in molecular evolution are exemplary of relative signicance debates in biology. One area that has received relatively little attention in philosophy of biology is the relationship between micro- and macro-evolution, and in particular, issues surrounding how hypotheses about change at and above the species level are tested. Plutynski (Speciation and Macroevolution) addresses this question, and reviews recent empirical and theoretical work on speciation, the punctuated equilibrium debate, and questions about the disparity and evolvability. Finally, Godfrey-Smith and Wilkins (Adaptationism) trace the history of the debate over adaptationist thinking, nicely demarcating different senses of adaptationism: empirical, explanatory, and methodological. In conclusion, they suggest a resolution to some of the controversy by illustrating how various alternatives might be resolved through careful attention to the grain at which evolutionary processes are being described. The section on Developmental Biology contains three important contributions. Kaplan (Phenotypic Plasticity and Reaction Norms) returns to the question of the relation between genotype and phenotype, already explored earlier by Lewontin. Once again the emphasis is on the complexity of this relation, which was largely ignored in classical genetics. Much of modern evolutionary theory was formulated at the genotypic level, ignoring the complexities of organismic development. The received view is that development can be put in a black box and phenotypic change tracked by recording changes at the genotypic level. However, it has long been recognized that, eventually, to understand the evolution of phenotypes, we must understand how developmental mechanisms have evolved. The past decade has seen a lot of excitement in evolutionary developmental biology, which many biologists now hold as nally sahotra sarkar and anya plutynski

23. xxiii successfully integrating evolutionary biology and studies of development. Amundson (Development and Evolution) puts these studies in historical perspective, analyzing the long, sometimes idiosyncratic, and largely unsuccessful past attempts to integrate the two disciplines. It is an open question whether the near future will be much different from the past. In Explaining the Ontogeny of Form: Philosophical Issues, Love provides a survey of issues surrounding the explanation of the ontogeny of form. He provides a philosophical framework for approaching different kinds of explanations in developmental biology, and addresses a variety of related epistemological and onto- logical issues; among them: representation, explanation, typology, individuality, model systems, and research heuristics. The next section (Medicine) takes up the relatively underexplored eld of health and disease. One area that has received relatively little attention among philosophers of biology is immunology. Howes (Self and Nonself) considers how philosophers can play a critical role in analyzing the conceptual foundations and empirical justications of different models of self and nonself deployed in immunology. Murphy (Health and Disease) considers objectivist, constructivist, and revisionist perspectives on health and disease, and focuses his discussion on the role of norms in judgments concerning mental illness. The Ecology section summarizes much of the recent work on the philosophy of ecology, another area of the philosophy of biology that is receiving increased attention in recent years. Perhaps the most theoretically mature part of ecology is population ecology, and Colyvan (Population Ecology) summarizes the philosophical work on the subject, showing how this is a fertile area to explore questions such as the role of laws and theories in biology. Justus (Complexity, Diversity, and Stability) turns to a central issue in community ecology, whether there is any relation between diversity and stability. He shows how the concepts of diversity and stability (and, also, though to a lesser extent, complexity) can be interpreted in a variety of inconsistent ways, making it almost impossible to answer this question. Inthecontextofourincreasingconcernfortheenvironment,Peacock(Ecosystems) describes recent thinking on ecosystems, including work done within science, and philosophically intriguing ideas at the fringe of science such as the Gaia hypothesis. Turning to conservation biology, Norton (Biodiversity and Conservation) shows how the concept of biodiversity is both descriptive (capturing some feature of habitats) and normative (reecting the values people have which make them want to preserve nature). He also embeds philosophical discussions of biodiversity in the context of environmental policy. The next section turns to mental and cultural life (Mind and Behavior), about which there is perhaps more scientic controversy than in any other area explored in depth by philosophers of biology. Grifths (Ethology, Sociobiology, and Evolutionary Psychology) gives a historical analysis that shows the deep connection between mid- twentieth-century ethology, human sociobiology, and contemporary Evolutionary Psychology. He notes that, while there is no reason to doubt that mental features are results of biological and cultural evolution, the research program of contemporary Evolutionary Psychology makes many controversial assumptions that should be scrutinized carefully. Alexander (Cooperation) takes up recent approaches to the evolution of cooperative behavior including the many applications of game theory. introduction

24. xxiv Finally, Bickerton (Communication and Language) explores what we do and do not know about the emergence and evolution of human language and notes both the analogies and disanalogies between language and animal communication systems. The nal section (Experimentation, Theory, and Themes) takes up a variety of general issues in the philosophy of biology, ranging from metaphysical issues about how to dene life, or whether there are biological laws, to epistemological issues about how biologists investigate the living world. Bedau (What is Life?) explores the variety of attempts to set out conditions for life, and discusses how and why this question has become especially pressing with recent research into articial life. Weber (Experimentation) analyzes the special difculties and characteristics of experimental work in biology. He considers the roles of model organisms, the limitations and advan- tages of laboratory work in biology, and the nature of evidence and objectivity in the biological sciences. Many philosophers hold that biology is not at all like physics insofar as there are no laws of biology; however, Lange (Is Biology Like Physics?) argues to the contrary. He considers the objection that laws of biology are not exceptionless and non-acciden- tal, and argues, using a number of different examples, that lawful generalizations are an integral part of evolutionary biology. While it is uncontroversial that models and modeling are central to empirical and theoretical work in all branches of biology, philosophers do not agree on what a model is. Odenbaugh (Models) reviews philosophical work on models, starting with the logical empiricists, explaining the subtle differences between the syntactic and semantic view of theories, and discusses a variety of historical and recent work on models and metaphors, and models as mediators between theory and data in the biological sciences. It is hard to imagine biology without talk of functions but there is little philosophical agreement on what a function is. Garson (Function and Teleology) gives a comprehensive review of the philosophical literature on functions, from etiological to conse- quentialist theories of function, and concludes with a defense of pluralist and context-dependent approaches to assignments of function. Yet another contentious issue in philosophy of biology has been the claim whether biological facts are reducible to molecular chemical or physical facts. Rosenberg (Reductionism in Biology) takes a radical stance on this question, arguing that while the reducibility of theories, as the logical empiricists understood it, is implausible, generalizations in functional biology can and should be reduced, in the sense of being completed, corrected, made more precise or otherwise deepened by fundamental explanations in molecular biology. References Beckner, M. (1959). The biological way of thought. New York: Columbia University Press. Brandon, R. (1982). The levels of selection. In P. Asquith & T. Nickles (Eds). Philosophy of Science Association Proceedings, 1, 31522. Carnap, R. (1958). Introduction to symbolic logic and its applications. New York: Dover Publications. Dobzhansky, T. (1973). Nothing in biology makes sense except in the light of evolution. American Biology Teacher, 35, 1259. sahotra sarkar and anya plutynski

25. xxv Driesch, H. (1929). Man and the universe. London: Allen & Unwin. Flew, A. (1984). Darwinian evolution. London: Paladin. Godfrey-Smith, P. (2004). Genes do not encode information for phenotypic traits. In C. Hitchcock (Ed.). Contemporary debates in the philosophy of science (pp. 275289). Oxford: Blackwell. Goudge, T. A. (1961). Ascent of life: a philosophical study of the theory of evolution. Toronto: University of Toronto Press. Haldane, J. B. S. (1936). Some principles of causal analysis in genetics. Erkenntnis, 6, 34657. Haldane, J. B. S. (1939). The Marxist philosophy and the sciences. New York: Random House. Haldane, J. S. (1929). The sciences and philosophy. Garden City, NY: Doubleday, Doran and Co. Haldane, J. S. (1931). The philosophical basis of biology. London: Hodder & Stoughton. Hogben, L. (1930). The nature of living matter. London: Kegan Paul, Trench, Trubner. Hull, D. (1965, a, b). The effect of essentialism on taxonomy two thousand years of stasis, Parts 1, 2. British Journal for the Philosophy of Science, 15, 314326, February; 16, 118, May. Hull, D. (1967). Certainty and circularity in evolutionary taxonomy. Evolution, 21, 17418. Hull, D. (1968). The operational imperative: sense and nonsense in operationism. Systematic Zoology, 17, 43857. Hull, D. (1972). Reduction in genetics biology or philosophy? Philosophy of Science, 39, 491 9. Hull, D. (1974). Philosophy of biological science. Englewood Cliffs, NJ: Prentice Hall. Hull, D. (1976). Are species really individuals? Systematic Zoology, 25, 17491. Hull, D. (1981). Reduction and genetics. The Journal of Medicine and Biology, 6, 12540. Kitcher, P. (1982). Genes. British Journal for the Philosophy of Science, 33, 33759. Kitcher, P. (1984). 1953 and all that: a tale of two sciences. Philosophical Review, 93, 33574. Lewontin, R. C. (1970). The units of selection. Annual Review of Ecology and Systematics, 1, 1 18. Maynard Smith, J. (1976). Group selection. Quarterly Review of Biology, 61, 27783. Nagel, E. (1949). The meaning of reduction in the natural sciences. In R. C. Stauffer (Ed.). Science and civilization (pp. 99135). Madison: University of Wisconsin Press, Nagel,E.(1951).Mechanisticexplanationandorganismicbiology.PhilosophyandPhenomenological Research, 11, 32738. Nagel, E. (1961). The structure of science. New York: Harcourt, Brace and World. Nagel, E. (1977). Teleology revisited. Journal of Philosophy, 74, 261301. Popper, K. (1974). Scientic reduction and the essential incompleteness of all science. In F. Ayala and T. Dobzhansky (Eds). Studies in the philosophy of biology: reduction and related problems (pp. 25984). Berkeley: University of California Press. Rheinberger, H.-J. (1993). Experiment and orientation: early systems in vitro protein synthesis. Journal of the History of Biology, 26, 44371. Rheinberger, H.-J. (1997). Experimental complexity in biology: some epistemological and historical remarks. Philosophy of Science, 64(4), S24554. Rosenberg, A. (1985). The structure of biological science. Cambridge/New York: Cambridge University Press. Ruse, M. (1976). Reduction in genetics. Boston Studies in the Philosophy of Science, 32, 63151. Sarkar, S. (1989). Reductionism and molecular biology: a reappraisal. PhD Dissertation, Department of Philosophy, University of Chicago. Sarkar, S. (1996). Biological information: a sceptical look at some central dogmas of molecular biology. In S. Sarkar (Ed.). The philosophy and history of molecular biology (pp. 187201). Dordrecht: Kluwer. Sarkar, S. (2005). Molecular models of life: philosophical papers on molecular biology. Cambridge, MA: MIT Press. Schaffner, K. F. (1967a). Approaches to reduction. Philosophy of Science, 34, 13747. introduction

26. xxvi Schaffner, K. F. (1967b). Antireductionism and molecular biology. Science, 157, 6447. Schaffner, K. F. (1969). The WatsonCrick model and reductionism. British Journal for the Philosophy of Science, 20, 32548. Schaffner, K. F. (1976). Reductionism in biology: prospects and problems. Philosophy of Science Association Proceedings, 1974, 613632. Scriven, M. (1959). Explanation and prediction. Science, 130, 47782. Sober, E. (1984). The nature of selection. Cambridge: MIT Press. Sober, E. R. (1988). Reconstructing the past: parsimony, evolution, and inference. Cambridge, MA: MIT Press, Bradford Books. Sterelny, K. and Grifths, P. E. (1999). Sex and death: an introduction to philosophy of biology. Chicago: University of Chicago Press. Wimsatt, W. (1971). Function, organization, and selection. Zygon: Journal of Religion and Science, 6, 16873. Wimsatt, W. (1972). Teleology and the logical structure of function statements. Studies in History and Philosophy of Science, 3, 180. Wimsatt, W. C. (1976). Reductive explanation: a functional account. Boston Studies in the Philosophy of Science, 32, 671710. Wimsatt, W. (1980). Reductionistic research strategies and their biases in the units of selection controversy. In T. Nickles (Ed.). Scientic discovery: case studies (pp. 21359). Boston: Reidel. Woodger, J. H. (1929). Biological principles. Cambridge: Cambridge University Press. Woodger, J. H. (1937). The axiomatic method in biology. Cambridge: Cambridge University Press. Woodger, J. H. (1952). Biology and language. Cambridge: Cambridge University Press. sahotra sarkar and anya plutynski

27. Part I Molecular Biology and Genetics

28. 3 Chapter 1 Gene Concepts hans-jrg rheinberger and staffan mller-wille 1. Introduction There has never been a generally accepted denition of the gene in genetics. There exist several, different accounts of the historical development and diversication of the gene concept. Today, along with the completion of the human genome sequence and the beginning of what has been called the era of post-genomics, genetics is again expe- riencing a time of conceptual change, with some even suggesting that the concept of the gene be abandoned altogether. As a consequence, the gene has become a hot topic in philosophy of science around which questions of reduction, emergence, or superve- nience are debated. So far, however, all attempts to reach a consensus regarding these questions have failed. The concept of the gene emerging out of a century of genetic research has been and continues to be, as Raphael Falk has reminded us, a concept in tension (Falk, 2000). Yet, despite this apparently irreducible diversity, there can be little doubt that the idea of the gene has been the central organizing theme of twentieth century biology, as Lenny Moss put it (Moss, 2003, p.xiii; see also Keller, 2001). The layout of this chapter will be largely historical. We will look at genes as epistemic objects. This means that we will not only relate established denitions of the gene, but rather analyze the processes in the course of which they became and still are being determined by changing experimental practices and experimental systems. After having thus established a rich historical panorama of gene concepts, some more general philosophical themes will be addressed, for which the gene has served as a convenient handle in discussion, and which revolve around the topic of reduction. Before dealing with the historical stages of the gene concepts tangled development, it will be useful to have a short look at its nineteenth-century background. It was only in the nineteenth century that heredity became a major biological problem (Gayon, 2000; Lpez Beltrn, 2004; Mller-Wille & Rheinberger, 2007), and with that the question of the material basis of heredity. In the second half of the nineteenth century, two alternative frameworks were proposed to deal with this question. The rst one conceived of heredity as a force the strength of which accumulated over generations, and which, as a measurable magnitude, could be subjected to statistical analysis. This concept was particularly widespread among nineteenth-century breeders (Gayon &

29. hans-jrg rheinberger and staffan mller-wille 4 Zallen, 1998) and inuenced Francis Galton and the so-called biometrical school (Gayon, 1998, pp.10546). The second saw heredity as residing in matter that was transmitted over the generations. Two major trends in this tradition are to be differen- tiated here. One of them regarded hereditary matter as particulate and amenable to breeding analysis. Charles Darwin called the presumed hereditary particles gemmules; Hugo de Vries, pangenes; Gregor Mendel, elements. None of these authors, however, associated these particles with a particular hereditary substance. They all thought that hereditary factors consisted of the stuff that the body of the organism is made of. A second category of biologists in the second half of the nineteenth century, to whom Carl Naegeli and August Weismann belonged, distinguished the body substance, the tro- phoplasm or soma, from a specic hereditary substance, the idioplasm, or germ-plasm, which was assumed to be responsible for intergenerational hereditary continuity. However, they took this idioplasmic substance as being not less particulate, but rather highly organized (Robinson, 1979; Churchill, 1987). Mendel stands out among these biologists. He is generally considered as the precur- sor to twentieth-century genetics (see, however, Olby, 1979). As Jean Gayon has argued, his 1866 paper (Mendel, 1866) attacked heredity from a wholly new angle, interpreting it not as a measurable magnitude, as the biometrical school did at a later stage, but as a structure in a given generation to be expressed in the context of specic crosses. This is why Mendel applied a calculus of differences, that is, combinatorial mathematics, to the resolution of hereditary phenomena (Gayon, 2000, pp.778). With that, he also introduced a new formal tool for the analysis of hybridization experiments: the selection of discrete character pairs (Mller-Wille & Orel, 2007). 2. The Gene in Classical Genetics The year 1900 is generally considered as the annus mirabilis that gave birth to a new discipline:genetics.Duringthatyear,threebotanists,HugodeVries,CarlCorrens,andErich Tschermak,reportedontheirbreedingexperimentsofthelate1890sandclaimedtohave conrmed the regularities that Mendel had already presented in his seminal paper (Olby, 1985, pp.10937). In their experimental crosses with Zea mays, Pisum, and Phaseolus, they observed that the elements responsible for pairs of alternative traits segregated ran- domly, but in a statistically signicant ratio, in the second lial generation (Mendels law of segregation), and that different pairs of these elements were transmitted independently from each other (Mendels law of independent assortment). The additional observation, that sometimes several elements behaved as if they were linked, contributed to the hypothesis soon promoted by Walter Sutton and by Theodor Boveri that these elements were located in groups on the different chromosomes of the nucleus. Thus the chromosome theory of inheritance assumed that the regularities of character transmission were grounded in the facts of cytomorphology (Coleman, 1965; Martins, 1999). Despite initial resistance from the biometrical school (Provine, 1971; MacKenzie & Barnes, 1979) awareness rapidly grew that the possibility of independent assortment of discrete hereditary factors, based on the laws of probability, was to be seen as the very cornerstone of a new paradigm of heredity (Kim, 1994). This went together, after an initial period of conation by the unit-character fallacy (Carlson,

30. gene concepts 5 1966, ch. 4), with the establishment of a categorical distinction between genetic factors on the one hand and characters on the other. The masking effect of dominant traits over recessive ones and the subsequent reappearance of recessive traits were particularly instrumental in stabilizing this distinction (Falk, 2001). Toward the end of the rst decade of the twentieth century, after William Bateson had coined the term genetics for the emerging new eld of transmission studies in 1906, Wilhelm Johannsen codied this distinction by introducing the notions of genotype and phenotype, respectively. In addition, for the elements of the genotype, he proposed the notion of gene. Johannsens distinction has profoundly marked all of twentieth-century genetics (Allen, 2002). We can safely say that it instituted the gene as an epistemic object to be studied within its proper epistemic space, and with that an exact, experimental doctrine of heredity (Johannsen, 1909, p.1) which concentrated on transmission only and not on the function and development of the organism in its environment. Some historians have spoken of a divorce of genetical from embryological concerns because of this separation (Allen, 1986; Bowler, 1989). Others hold that this separation was itself an expression of the embryological interests of early geneticists in their search for developmental invariants (Gilbert, 1978; Griesemer, 2000). Be that as it may, the result was that the relations between the two spaces, once separated by abstraction, were now experimentally elucidated in their own right (Falk, 1995). Michel Morange judged this rupture to be logically absurd, but historically and scientically necessary (Morange, 1998, p.22). Johannsen himself stressed that the genotype had to be treated as independent of any life history and thus as an ahistoric entity amenable to scientic scrutiny like the objects of physics and chemistry (Johannsen, 1911; see Churchill, 1974; Roll-Hansen, 1978a). Unlike most Mendelians, however, he remained convinced that the genotype would possess an overall architecture. He therefore had reservations with respect to its particulate character, and especially warned that the notion of genes for a particular character should always be used cautiously if not altogether be omitted (cf. Moss, 2003, p.29). Johannsen also clearly recognized that the experimental regime of Mendelian genetics neither required nor allowed any denite supposition about the material structure of the genetic elements. For him, the gene remained a concept completely free of any hypothesis (Johannsen, 1909, p.124). On this account, genes were taken as the abstract elements of an equally abstract space whose structure, however, could be explored through the visible and quantiable outcome of breeding experiments based on mutations of model organisms. This became the research program of Thomas Hunt Morgan and his group. From the early 1910s into the 1930s, the growing community of researchers around Morgan and their fol- lowers used mutants of the fruit y Drosophila melanogaster in order to produce a map of the fruit ys genotype in which genes, and alleles thereof, gured as genetic markers which occupied a particular locus on one of the four homologous chromosome pairs of the y (Kohler, 1994). The basic assumptions that allowed the program to operate were that genes were located in a linear fashion on the chromosomes, and that the frequency of recombination events between homologous chromosomes gave a measure of the distance between the genes, at the same time dening them as units of recombination (Morgan et al., 1915). In this practice, identiable aspects of the phenotype, assumed to be determined directly by genes, were used as indicators or windows for an outlook

31. hans-jrg rheinberger and staffan mller-wille 6 on the formal structure of the genotype. This is what Moss has termed the Gene-P (P standing for phenotype). Throughout his career, Morgan remained aware of the formal character of his program (Morgan, 1935, p.3). In particular, it did not matter if one-to-one, or more complicated relationships reigned between genes and traits. Morgan and his school were well aware that, as a rule, many genes were involved in the development of a particular trait, and that one gene could affect several characters. To accommodate this difculty and in line with their experimental regime, they embraced a differential concept of the gene. What mattered to them was the relationship between a change in a gene and a change in a trait, rather than the nature of these entities themselves. Thus the alteration of a trait could be causally related to a change in (or a loss of) a single genetic factor, even if it was plausible in general that a trait like eye-color was, in fact, determined by a whole group of variously interacting genes (Roll-Hansen, 1978b; Schwartz, 2000). The fascination of this approach consisted in the fact that it worked, if properly con- ducted, like a precision instrument. Population geneticists like Ronald A. Fisher, J. B. S. Haldane, and Sewall Wright could make use of that same abstract gene concept in developingelaboratemathematicalmodelsdescribingtheeffectsofevolutionaryfactorson the genetic composition of populations. As a consequence, evolution became re-dened as a change of gene frequencies in the gene pool of a population in what is commonly called the evolutionary, neo-Darwinian, or simply modern synthesis of the late 1930s (Dobzhansky, 1937) [See Darwinism and Neo-Darwinism]. Considered asadevelopmentalinvariant(Griesemer,2000),andsolelyobeyingtheMendelianlaws in its transmission from one generation to the next, the gene provided a kind of inertia principle against which the effects of both developmental (epistasis, inhibition, position effects, etc.) and evolutionary factors (selection, mutation, recombination, etc.) could be measured with utmost accuracy, assessed and accurately quantied (Gayon, 1995). Nevertheless,itbecametheconvictionofmanygeneticistsinthe1920s,amongthem Morgans student, Herman J. Muller, that genes had to be material particles. Muller saw genes as endowed with two properties: that of autocatalysis and that of heterocatalysis. Their autocatalytic function allowed them to reproduce as units of transmission and thus to connect the genotype of one generation to that of the next. Their heterocatalytic capabilities connected them to the phenotype, as functional units involved in the expression of a particular character. With his own experimental work, Muller added a signicant argument for the materiality of the gene, pertaining to a third property of the gene, itssusceptibilitytomutations.In1927,hereportedontheinductionofMendelianmuta- tionsinDrosophilabyusingX-rays.HeconcludedthattheX-raysmusthavealteredsome molecular structure in a permanent fashion. But the experimental practice of X-raying, which eventually gave rise to a whole industry of radiation genetics in the 1930s and 1940s, did not by itself open the path to the material characterization of genes as units of heredity (Muller, 1951, pp.956). Meanwhile, cytological work had also added credence to the materiality of genes, residing on chromosomes. During the 1930s, the cytogeneticist, Theophilus Painter, correlated formal patterns of displacement of genetic loci on Morganian chromosome maps with visible changes in the banding pattern of giant salivary gland chromosomes of Drosophila. Barbara McClintock was able to follow with her microscope the changes

32. gene concepts 7 translocations, inversions and deletions induced by X-rays in the chromosomes of Zea mays (maize) Corn. Simultaneously, Alfred Sturtevant, in his experimental work on the Bar eye effect in Drosophila at the end of the 1920s, had shown what came to be called a position effect: the expression of a mutation was dependent on the position of the corresponding gene on the chromosome. This nding stirred wide-ranging discussions about the heterocatalytic aspect of a gene. If a genes function depended on its position on the chromosome, it became questionable whether that function was stably connected to that gene at all, or as Richard Goldschmidt had assumed, whether physiological function was not determined by the organization of the genetic material (Goldschmidt, 1940; see also Dietrich, 2000). Thus far, all experimental approaches in the new eld of genetics had remained silent with respect to the two basic Mullerian aspects of the gene: its autocatalytic and its heterocatalytic function. Toward the end of the 1930s, Max Delbrck had the intu- ition that the question of autocatalysis, that is, replication, could be attacked through the study of phage. But the phage system, which he established throughout the 1940s, remained as formal as that of classical Drosophila genetics. Around the same time, Alfred Khn and his group, as well as Boris Ephrussi and George Beadle, using organ transplantations between mutant and wild type insects, opened a window on the space between the gene and its presumed physiological function. Studying the pigmentation of insect eyes, they realized that genes did not directly give rise to physiological sub- stances, but that they obviously rst initiated what Khn termed a primary reaction leading to ferments or enzymes, which in turn catalyzed particular steps in metabolic reaction cascades. Khn viewed his experiments as the beginning of a reorientation of what he perceived to be the preformationism of transmission genetics of his day. He pleaded for an epigenetics that would combine genetic, developmental, and physiological analyses to dene heterocatalysis as the result of an interaction of two reaction chains, one leading from genes to particular ferments, and the other leading from one metabolic intermedi- ate to the next by the intervention of these ferments, thus resulting in complex epigenetic networks (Khn, 1941, p.258; Rheinberger, 2000a). On the other side of the Atlantic, George Beadle and Edward Tatum, working with cultures of Neurospora crassa, codied the rst of these relations into the one-geneone-enzyme hypothesis. But for Khn, as well as to Beadle and Tatum, the material character of genes and the way these putative entities gave rise to primary products remained elusive and beyond the reach of experimental analysis. The gene in classical genetics was already far from being a simple concept corresponding to a simple entity. Conceiving of the gene as a unit of transmission, recombination, mutation, and function, classical geneticists combined various aspects of hereditary phenomena. Well into the 1940s, only proteins were thought to be complex enough to perform these tasks. But owing to the lack of knowledge about the material nature of the gene, gene conceptions remained largely formal and operationalist, i.e., were substantiated indirectly by the successes achieved in explaining and predicting experimental results. This lack of a synthetic understanding of the gene notwithstand- ing, the mounting successes of the various research strands associated with classical genetics led to a hardening of the belief in the gene as a discrete, material entity (Falk, 2000, pp.3236).

33. hans-jrg rheinberger and staffan mller-wille 8 3. The Gene in Molecular Genetics The enzyme view of gene function, as envisaged by Khn and by Beadle and Tatum, gave the idea of genetic specicity a new twist and helped to pave the way to the molecularization of the gene. The same can be said about the ndings of Oswald Avery and his colleagues in the early 1940s. They puried the deoxyribonuleic acid (DNA) of one strain of bacteria, and demonstrated that it was able to transmit the infectious characteristics of that strain to another, harmless one. Yet the historical path that led to an understanding of the nature of the molecular gene was not a direct follow-up of classical genetics. It was rather embedded in an overall molecularization of biology driven by the application of newly developed physical and chemical methods and instruments to problems of biology. Among these methods were ultracentrifugation, X-ray crystallography, electron microscopy, electrophoresis, macromolecular sequencing, and radioactive tracing. The transition also relied upon use of comparatively simple model organisms like unicellular fungi, bacteria, viruses, and phage. A new culture of physically and chemically instructed in vitro biology ensued, which in large part no longer rested on the presence of intact organisms in a particular experi8mental system (Rheinberger, 1997). For the development of molecular genetics in the narrow sense, three lines of experimental inquiry proved to be crucial. They were not connected to each other when they gained momentum in the late 1940s, but they happened to merge at the beginning of the 1960s, giving rise to a grand new picture. The rst of these developments was the elucidation of the structure of DNA as a macromolecular double helix by Francis Crick and James D. Watson in 1953. This work was based on chemical information about base composition of the molecule provided by Erwin Chargaff, on data from X-ray crystallography produced by Rosalind Franklin and Maurice Wilkins, and on mechanical model building as developed by Linus Pauling. The result was a picture of a nucleic acid double strand, the four bases (Adenine, Thymine, Guanine, Cytosine) of which formed complementary pairs (A-T, G-C) that could be arranged in all possible combina- tions into linear sequences. At the same time, that molecular model suggested an elegant mechanism for the duplication of the molecule. Opening the strands and synthesizing two new strands complementary to each would sufce to create two identical helices from one. Thus, the structure of the DNA double helix had all the characteristics that were to be expected from a molecule serving as an autocatalytic hereditary entity (Chadarevian, 2002). The second line of experiment that formed molecular genetics was the in vitro characterization of the process of protein biosynthesis to which many biochemical researchers contributed, among them Paul Zamecnik, Mahlon Hoagland, Paul Berg, Fritz Lipmann, Marshall Nirenberg, and Heinrich Matthaei. It started in the 1940s largely as an effort to understand the growth of malignant tumors. During the 1950s, it became evident that the process required a ribonucleic acid (RNA) template that was originally thought to be part of the microsomes on which the assembly of amino acids was seen to take place. It turned out that the process of amino acid condensation was mediated by a transfer molecule with the characteristics of a nucleic acid and the capac- ity to carry an amino acid. The ensuing idea that it was a linear sequence of ribonucleic acid derived from one of the DNA strands that directed the synthesis of a linear sequence

34. gene concepts 9 of amino acids, or a polypeptide, and that this process was mediated by an adaptor molecule, was soon corroborated experimentally. The relation between these two classes of molecules was found to be ruled by a nucleic acid triplet code: three bases at a time specied one amino acid (Rheinberger, 1997; Kay, 2000). Hence, the sequence hypothesis and the Central Dogma of molecular biology, which Francis Crick formulated at the end of the 1950s: In its simplest form [the sequence hypothesis] assumes that the specicity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein. [The central dogma] states that once information has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. (Crick, 1958, pp.1523) With these two fundamental assumptions, a new view of biological specicity came into play (Sarkar, 1996). In its center stands the transfer of molecular order from one macromolecule to the other. In one molecule the order is preserved structurally; in the other it becomes expressed and provides the basis for a biological function carried out by a protein. This transfer process became characterized as molecular information transfer [See Biological Information]. Henceforth, genes could be seen as stretches of deoxyribonucleic acid (or ribonucleic acid in certain viruses) carrying the information for the assembly of a particular protein. Both molecules were thus thought to be co- linear. In the end, both the fundamental properties that Muller had required of genes, namely autocatalysis and heterocatalysis, were perceived as relying on one and the same stereochemical principle, respectively: The base complementarity between nucleic acid building blocks C-G and A-T (U in the case of RNA) was responsible both for the faithful duplication of genetic information in the process of replication, and, via the genetic code, for the transformation of genetic information into biological function through transcription and translation. The code, as well as the mechanisms of transcription and translation, turned out to be nearly universal for all living beings. The genotype was thus recongured as a universal repository of genetic information, sometimes also addressed as a genetic program. Talk of DNA as embodying genetic information, as being the blueprint of life, which governs public discourse to this day, emerged from a peculiar conjunction of the physical and the life sciences during World War II, with Erwin Schrdingers What is Life? as a source of inspiration (Schrdinger, 1944), and cybernetics, a discipline engaged in the study of complex systems and their self- regulation. It needs to be stressed, however, that initial attempts to crack the DNA code by purely cryptographic means soon ran into a dead end. In the end it was bio- chemists who unraveled the genetic code by the advanced tools of their discipline (Judson, 1996; Kay, 2000). For the further development of the notion of DNA as a program, we have to con- sider an additional third line of experiment, aside from the elucidation of DNA structure and the mechanisms of protein synthesis. This line of experiment came out of a fusion of bacterial genetics with the biochemical characterization of an inducible system of sugar metabolizing enzymes. It was largely the work of Franois Jacob and Jacques Monod and led, at the beginning of the 1960s, to the identication of messenger RNA

35. hans-jrg rheinberger and staffan mller-wille 10 as the mediator between genes and proteins, and to the description of a regulatory model of gene activation, the so-called operon model, in which two classes of genes became distinguished: One class was the structural genes. They were presumed to carry the structural information for the production of particular polypeptides. The other class was the regulatory genes. They were assumed to be involved in the regulation of the expression of structural information. A third element of DNA involved in the regulatory loop of an operon was a binding site, or signal sequence, that was not transcribed at all. These three elements, structural genes, regulatory genes, and signal sequences, provided the framework for viewing the genotype as an ordered, hierarchical system, as a genetic program, as Jacob contended, not without adding that it was a very peculiar program, namely one that needed its own products for being executed (Jacob, 1976, p.297). If we take that view seriously, although the whole conception looks like a circle (Keller, 2000), it is in the end the organism which interprets or recruits the structural genes by activating or inhibiting the regulatory genes that control their expression. The operon model of Jacob and Monod marked the precipitous end of the simple, informational concept of the molecular gene. Since the beginning of the 1960s, the picture of gene expression has become vastly more complicated (see Rheinberger, 2000b, and Genomics and Proteomics). Moreover, most genomes of higher organisms appear to contain huge DNA stretches to which no function can as yet be assigned. Finally, the non-coding, but functionally specic, regulatory DNA-elements have proliferated: There exist promoter and terminator sequences; upstream and down- stream activating elements in transcribed or non-transcribed, translated or untrans- lated regions; leader sequences; externally and internally transcribed spacers before, between, and after structural genes; interspersed repetitive elements and tandemly repeated sequences such as satellites, LINEs (long interspersed sequences), and SINEs (short interspersed sequences) of various classes and sizes (for an overview see Fischer, 1995). As far as transcription, i.e., the synthesis of an RNA copy from a sequence of DNA, is concerned, overlapping reading frames have been found on one and the same strand of DNA, and protein coding stretches have been found to derive from both strands of the double helix. On the level of modication after transcription, the picture has become equally complicated. Soon it was realized that DNA transcripts such as transfer RNA and ribosomal RNA had to be trimmed and matured in a complex enzymatic manner to become functional molecules, and that messenger RNAs of eukaryotes underwent extensive post-transcriptional modication before they were ready to go into the translation machinery. In the 1970s, to the surprise of everybody, molecular biologists had to acquaint themselves with the idea that eukaryotic genes were composed of modules, and that, after transcription, introns were cut out and exons spliced together in order to yield a functional message. The gene-in-pieces was one of the rst major scientic offshoots of recombinant DNA technology, and this technology has since continued to be useful for exploring unanticipated vistas on the genome. A spliced messenger sometimes may comprise a fraction as little as 10 percent or less of the primary transcript. Since the late 1970s, molecular biologists have become familiar with various kinds of RNA splicing: autocatalytic self-splicing, alternative splicing of one single transcript to yield different messages; and even trans-splicing of different primary transcripts to yield

36. gene concepts 11 one hybrid message. Finally, yet another mechanism, or rather, class of mechanisms has been found to operate on the level of RNA transcripts. It is called mess